Hormones and neurotransmitters can modulate electrical activity of peripheral olfactory receptor neurons (Eisthen et al., 1996; Lucero et al., 1996). This suggests that the olfactory output may be subject to some form of initial processing. Analogous to the way the other sensory systems (i.e. the retina, vestibular, and gustatory systems) have been shown to modulate sensory input, olfactory information may be modified before it leaves the periphery. This project is focused on peripheral modulation of olfactory neurons by endogenous neuroactive compounds. There are many possible avenues through which internal agents could modify the activity of ORNs; the substances in the mucus bathing the dendritic ends of the cells, the neuropeptides and neurotransmitters in the olfactory epithelium, even possible feedback from the olfactory bulb. Preliminary experiments in this laboratory have shown that gonadotropin-releasing hormone (GnRH) and dopamine can modulate voltage-activated currents in Necturus ORNs. Thus both of these substances may serve as neuromodulators of olfactory neurons. The goals of this study are to identify the voltage-activated currents that are modulated by GnRH and dopamine in Necturus olfactory neurons and to characterize the second messenger systems that mediate each of these effects. In addition the effects of these two potential neuromodulators on the microvillar and ciliated olfactory neurons will be determined and compared.